Exploration of Core Genes Signature and Prognostic Implication for Ductal Carcinoma In Situ of the Breast

Abstract Background: Following the implementation of breast screening programs, the occurrence of DCIS has risen as an early form of neoplasm. Although the prognosis is good, 20-50% of DCIS patients will develop invasive ductal carcinoma (IDC) if they are not handled. It is important to look for promising biomarkers for predicting DCIS prognosis.Methods: The Gene Expression Omnibus (GEO) database provided three microarray profile datasets. The expression of genes that differed between DCIS and normal tissue was investigated. To describe the biological role and intrinsic process pathway, enrichment analysis was used. The Cancer Genome Atlas Breast Cancer Dataset was used to classify the hub genes and further verify the findings using CytoHubba and MCODE, two Cytoscape plugins. The prognostic ability of the core genes signature was determined through time-dependent receiver operating characteristic (ROC), Kaplan-Meier survival curve, Oncomine databases, and UALCAN databases. In addition, in proliferation assays, the prognostic value of core genes was verified.Results: We identified 217 common DEGs, with 101 up-regulated and 138 down-regulated genes in the present study. The top genes were obtained from the PPI network (protein-protein interaction). For DCIS prognosis prediction, a novel six gene signature (including GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed. Centered on the TCGA cohort, the ROC curve showed strong results in prognosis prediction. The six core genes signature is often overexpressed in DCIS, which has a weak prognosis. Furthermore, transfected with small interfering RNAs, downregulation of core gene expression significantly inhibits breast cancer cell proliferation, implying a great potential for using core genes in DCIS prognosis.Conclusions: The six core genes signature for promising DCIS biomarkers was validated in our research, which may assist in clinical decision-making for individual care.